Loss of Serglycin Promotes Primary Tumor Growth and Vessel Functionality in the RIP1-Tag2 Mouse Model for Spontaneous Insulinoma Formation

PLoS One. 2015 May 15;10(5):e0126688. doi: 10.1371/journal.pone.0126688. eCollection 2015.


The serglycin proteoglycan is mainly expressed by hematopoietic cells where the major function is to retain the content of storage granules and vesicles. In recent years, expression of serglycin has also been found in different forms of human malignancies and a high serglycin expression level has been correlated with a more migratory and invasive phenotype in the case of breast cancer and nasopharyngeal carcinoma. Serglycin has also been implicated in the development of the tumor vasculature in multiple myeloma and hepatocellular carcinoma where reduced expression of serglycin was correlated with a less extensive vasculature. To further investigate the contribution of serglycin to tumor development, we have used the immunocompetent RIP1-Tag2 mouse model of spontaneous insulinoma formation crossed into serglycin deficient mice. For the first time we show that serglycin-deficiency affects orthotopic primary tumor growth and tumor vascular functionality of late stage carcinomas. RIP1-Tag2 mice that lack serglycin develop larger tumors with a higher proliferative activity but unaltered apoptosis compared to normal RIP1-Tag2 mice. The absence of serglycin also enhances the tumor vessel functionality, which is better perfused than in tumors from serglycin wild type mice. The presence of the pro-angiogenic modulators vascular endothelial growth factor and hepatocyte growth factor were decreased in the serglycin deficient mice which suggests a less pro-angiogenic environment in the tumors of these animals. Taken together, we conclude that serglycin affects multiple aspects of spontaneous tumor formation, which strengthens the theory that serglycin acts as an important mediator in the formation and progression of tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Disease Models, Animal
  • Disease Progression
  • Female
  • GTPase-Activating Proteins / genetics*
  • Insulinoma / genetics*
  • Insulinoma / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multiple Myeloma / genetics
  • Multiple Myeloma / pathology
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / pathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology*
  • Physiological Phenomena / genetics
  • Proteoglycans / genetics*
  • Vascular Endothelial Growth Factor A / genetics
  • Vesicular Transport Proteins / genetics*


  • GTPase-Activating Proteins
  • Proteoglycans
  • Ralbp1 protein, mouse
  • Vascular Endothelial Growth Factor A
  • Vesicular Transport Proteins
  • serglycin

Grants and funding

Funding provided Swedish Cancer Society; Grant no. 120507; MR; http://www.cancerfonden.se/; the Swedish Research Council; Grant no. 90252201; MR; http://www.vr.se/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.